Ozempic and The Brain: The Dual Effect of Weight Loss Pills on Dopamine, Addiction, and Depression

Ozempic, used to treat diabetes and aid in weight loss, can also affect the brain. It acts on dopamine, a neurotransmitter linked to pleasure and motivation. In some people, it can help reduce compulsive behaviors, such as addictions. But in others, especially those who already have low dopamine, it can worsen mood and even cause depressive symptoms. Therefore, its use must be done with caution and under medical supervision.

Ozempic, whose active ingredient is semaglutide, is a medication that has gained great prominence in recent years, mainly in the treatment of type 2 diabetes and obesity. It belongs to a class of medications called glucagon-like peptide-1 receptor agonists, or GLP-1R.

In addition to helping control blood sugar and promoting weight loss, there is growing interest in the scientific community in understanding how this type of medication can influence other aspects of health, such as behavior, mood and even substance dependence.

The focus of this study was to explore possible connections between the use of GLP-1R agonists, such as Ozempic, and their effects on the brain, especially in relation to the regulation of dopamine, which is a neurotransmitter essential for the reward, motivation and pleasure systems.

The research investigated how GLP-1R agonists affect people with disorders linked to the use of substances, such as alcohol and drugs, known as Alcohol Use Disorder (AUD) and Substance Use Disorder (SUD).

These disorders are closely related to dopamine, as this chemical plays a central role in feelings of pleasure and reinforcement of behaviors, which contributes to the cycle of addiction.

The authors suggest that medications such as Ozempic may help reduce the excessive activity of dopamine (hyperdopaminergia), which is common in some addictive disorders.

However, they also warn that in people who already have low levels of dopamine (hypodopaminergic) these drugs can worsen the condition, leading to symptoms such as lack of motivation, apathy and, in extreme cases, suicidal thoughts.

This potential side effect raises important concerns, especially because there is an incorrect belief that these drugs automatically “balance” dopamine levels. In fact, their impact depends on the individual biological profile of each patient.

To further investigate this issue, the researchers genetically analyzed targets related to Ozempic, GLP-1R and enzymes involved in brain signaling processes.

They used a computational tool called STRING-MODEL to study 31 genes related to the action of the drug and also genes associated with the genetic risk of addictive behaviors, using a test called GARS (Genetic Addiction Risk Score).

The GARS test is a genetic test that analyzes variations in certain genes linked to the brain's reward system, mainly those that control dopamine, the substance related to pleasure and motivation.

The idea is to identify whether the person has a greater predisposition to develop addictive behaviors, such as dependence on alcohol, drugs, food or even gambling. GARS helps to understand whether someone's "reward brain" works differently, which can increase the risk of addiction.

Genetic analyses have indicated links between GLP-1R and several genes associated with depressive states and dopamine regulation, such as DRD3, BDNF, CREB1, CRH, IL6 and DPP4.

These genes are linked to processes that influence the body's mood, stress and inflammatory response, all factors that, when altered, can contribute to the development of depression.

This means that, although Ozempic can reduce the desire for substances in some people, in others it can negatively interfere with emotional balance and brain functions.

In conclusion, the researchers highlight that the use of GLP-1R agonists may have a “double effect”. On the one hand, these drugs have the potential to reduce compulsive behaviors related to drug addiction.

On the other hand, they may trigger or worsen depressive symptoms in people with a genetic predisposition to dopamine imbalances. This double effect makes it essential to conduct more clinical studies with real patients, so that we can better understand who can safely benefit from these drugs and who may be at risk.

The research points to the urgent need for a more personalized approach to prescribing these drugs, taking into account each individual’s genetic and neurochemical profile.

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In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and the Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicidal Ideation and Substance Use Disorder

Alireza Sharafshah, Kai-Uwe Lewandrowski, Mark S. Gold, Brian Fuehrlein, John Wesson Ashford, Panayotis K. Thanos, Gene Jack Wang, Colin Hanna, Jean Lud Cadet, Eliot L. Gardner, Jag H. Khalsa, Eric R. Braverman, David Baron, Igor Elman, Catherine A. Dennen, Abdalla Bowirrat, Albert Pinhasov, Edward J. Modestino, Paul R. Carney, Rene Cortese, Rossano Kepler Alvim Fiorelli, Sergio Schmidt, Aryeh R. Pollack, Rajendra D. Badgaiyan and Kenneth Blum

Current Neuropharmacology. Volume 23, Issue 8, 2025. Page: [974 - 995]

DOI: 10.2174/011570159X349579241231080602

Abstract

Glucagon-Like Peptide-1 Receptor (GLP1R) agonists have become widespread anti-obesity/diabetes pharmaceuticals in the United States. This article aimed to provide our current knowledge on the plausible mechanisms linked to the role of Ozempic (Semaglutide), which is generalized as one of the anti-addiction compounds.The effects of GLP1R agonists in Alcohol Use Disorder (AUD) and substance use disorder (SUD) are mediated, in part, through the downregulation of dopamine signaling. We posit that while GLP1R agonism could offer therapeutic advantages in hyperdopaminergia, it may be detrimental in patients with hypodopaminergia, potentially leading to long-term induction of Suicidal Ideation (SI). The alleged posit of GLP1 agonists to induce dopamine homeostasis is incorrect. This study refined 31 genes based on the targets of Ozempic, GLP1R, and related enzymes for SI and 10 genes of the Genetic Addiction Risk Score (GARS) test. STRING-MODEL refined 29 genes, and further primary analyses indicated associations of GLP1R with DRD3, BDNF, CREB1, CRH, IL6, and DPP4. In-depth silico enrichment analysis revealed an association between candidate genes and depressive phenotypes linked with dopaminergic signaling. Finally, through primary and in-depth silico analyses, we demonstrated multiple findings supporting that GLP1R agonists can induce depression phenotypes. Our findings suggest that associated polymorphisms seem to have overlapping effects with addictive behaviors of Reward Deficiency Syndrome (RDS) and dopamine regulation. Consequently, GLP1R agonists may represent a double-edged sword, potentially triggering both antiaddictive effects and SI by exacerbating depressive phenotypes. Thus, we encourage the scientific community to perform further empirical clinical studies to confirm this proposed pathway.